We evaluated the response of adult volunteers to a series of ts or cold adapted recombinants of influenza A virus. A/Victoria/75 ts-1(E) recombinants, with a 38 degrees C shut off temperature and ts lesions in RNA segments 1 and 5, retained some virulence for individuals who lacked immunity to the hemagglutinin and neuraminidase antigens of the virus. In contrast, a more temperature sensitive A/Victoria/75 ts-1A2 recombinant, with a 37 degrees C shut off temperature and ts lesions in RNA segments 1 and 2, was satisfactorily attenuated for doubly seronegative volunteers. Contrasting responses were observed with 2 ca recombinants; A/Scotland/74 ca retained some virulence, while A/Victoria/75 ca was satisfactorily attentuated.